alexa Adaptation to High Altitude Hypoxia Protects the Rat Heart Against Ischemia-induced Arrhythmias. Involvement of Mitochondrial KATPChannel


Journal of Clinical & Experimental Cardiology

Author(s): Girma Asemu

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The aim was to determine whether adaptation to chronic hypoxia protects the heart against ischemic arrhythmias and whether ATP-dependent potassium channels (KATP) play a role in the antiarrhythmic mechanism. Adult male rats were adapted to intermittent high altitude hypoxia (5000 m, 4 h/day) and susceptibility to ischemia-induced ventricular arrhythmias was evaluated in the Langendorff-perfused hearts subjected to either an occlusion of the coronary artery for 30 min or pre-conditioning by brief occlusion of the same artery prior to 30-min reocclusion. In separate groups, either a KATPblocker, glibenclamide (10 μ mol/l), or a mitochondrial KATPopener, diazoxide (50μ mol/l), were added to a perfusion medium 20 min before the occlusion. Adaptation to hypoxia reduced the total number of ventricular arrhythmias by 64% as compared with normoxic controls. Preconditioning by a single 3-min coronary artery occlusion was antiarrhythmic only in the normoxic group, while two occlusion periods of 5 min each were needed to pre-condition the hypoxic hearts. Glibenclamide increased the number of arrhythmias in the normoxic hearts from 1316±215 to 2091±187 (by 59%) and in the hypoxic group from 636±103 to 1777±186 (by 179%). In contrast, diazoxide decreased the number of arrhythmias only in the normoxic group from 1374±96 to 582±149 (by 58%), while its effect in the hypoxic group was not significant. It is concluded that long-term adaptation of rats to high altitude hypoxia decreases the susceptibility of their hearts to ischemic arrhythmias and increases an antiarrhythmic threshold of pre-conditioning. The mitochondrial KATPchannel, rather than the sarcolemmal KATPchannel, apears to be involved in the protective mechanism afforded by adaptation.

This article was published in J Mol Cell Cardiol and referenced in Journal of Clinical & Experimental Cardiology

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